The aim of the proposed investigation is to measure the pool size, tissue distribution and immunological performance of various species of lymphocytes in young, mature and senescent rats, and to develop a model system in which age-related changes in the immune capacity can be critically evaluated with respect to host resistance to cancer. Defined populations of antigen-reactive cells, specifically sensitized lymphocytes and cells which carry immunological memory would be prepared by cell chromatography from the thoracic duct lymph of either normal or specifically immunized donors. These would be studied in vitro or after transfer to normal syngeneic recipients. Radiolabeling techniques, monospecific antisera and immunogenetic markers would be used to trace the tissue disposition and fate of the transferred cells. The circulating pool of T or B cells into which the donor lymphocytes are diluted would also be measured. A study would be made of the response of aging rats to methylcholanthrene-induced sarcoma cells and the results correlated with age-related changes in the number and functional capacity of T and B cells as determined in experiments using conventional antigens. Finally, the impact of various immunotherapeutic and immunosuppressive agents on the cellular response to tumor-specific antigens would be analyzed with the purpose of determining the optimal conditions for bolstering the host's immune defenses.